As outlined in the request for applications (RFA-DA-04-002) to which we respond here, research that uses rapidly advancing neuro imaging technology to address the effects of drug exposure during development is much needed. We have chosen to investigate this important topic by focusing our efforts on three populations of children, those with prenatal exposure to methamphetamine (MA), those with prenatal exposure to alcohol, and normally developing children without prenatal exposure to drugs of abuse. We will study these populations using structural and functional magnetic resonance imaging, neurocognitive testing, longitudinal data collection, and novel image analyses techniques to assess the following specific aims. 1) To examine brain structural abnormality as a function of prenatal exposure to MA or alcohol, both cross-sectional and longitudinally. 2) To examine differences in brain functional activation between children and adolescents who were exposed to large amounts of MA or alcohol prenatally and those who were not exposed. 3) To examine differences between groups in cognitive functioning using a broad battery of neuropsychological testing instruments. These studies are of critical importance given that very little is known about the effects of prenatal exposure to MA on the developing brain, and MA abuse is rapidly escalating in the United States. Pregnant women are likely among the increased population using this illicit drug, placing an increased sense of importance on our understanding of the consequences of its abuse during pregnancy. To date, there are no published studies describing detailed structural brain abnormalities, functional activation disturbances, or neurocognitive deficits in children with prenatal MA exposure. By comparison, relatively more is known about the teratogenic effects of alcohol on the developing brain, but its abuse during pregnancy is still a significant health problem. The proposal to study two populations with prenatal exposure is critical to our better understanding of the specific neural impact of each drug. This is because the alcohol-exposed individuals will be a better comparison group to assess the effects of prenatal MA exposure, given likely similarities between the groups in pre- and post-natal environments (i.e., nutrition, socioeconomic status, maternal smoking during pregnancy) relative to children without prenatal exposure who are typically studied as a comparison group.